A dramatic escalation in the prevalence of tobacco use and addiction in developing countries has been documented, increasing the threat of grave consequences for health and for sustainable economic development in these countries. In order to slow this epidemic, it is important to identify psychosocial and biochemical factors that promote and maintain this addiction, and to subsequently develop effective methods to address it. The situation in Yemen and in neighboring countries is particularly grim and complicated by the concurrent use of khat, a psychostimulant drug widely used by both men and women. Yemen is a low-income country with unique strategic characteristics, being centrally located within a group of culturally and linguistically similar countries in need of efforts to reduce tobacco use. The long-term goal of this proposal is to develop a multidisciplinary research program focusing on biobehavioral mechanisms of tobacco addiction and the concurrent use of khat in Yemen. The specific goal of this FIRCA proposal is to determine hormonal, hemodynamic, and mood changes during rest and in response to acute behavioral stressors among dependent tobacco users and non-users who are or are not regular khat users. The design will include 4 groups: tobacco and khat users, tobacco users only, khat users only, and those who do not use either drug. Measures will be collected in two counterbalanced sessions conducted on two separate days, after abstinence or ad libitum tobacco use. Ambulatory cortisol and self-report measures of withdrawal symptoms will also be obtained during the 24-hour period prior to each session. We will include men and women, and will, therefore, examine gender differences in responses to psychological stress among tobacco and khat users. The project will represent a first stage towards developing a sustainable research program that will focus on understanding and combating tobacco addiction and concurrent use of khat in Yemen and the surrounding region. The results will improve our basic understanding of concurrent addictions and subsequently help us develop effective methods for prevention and treatment of these addictions. This work is also relevant to research focusing on concurrent addictive behaviors in other countries. Successful efforts to reduce the tobacco epidemic and to reduce concurrent use of other substances will have a significant positive impact on global health and security.